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Updated: Sep 16, 2025
Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
Effects of prenatal azithromycin exposure at different stages, doses, and treatment durations on placental
Wen Zhong1, Yuting Chen2, Xiaomeng Zha3
1Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
Introduction:
Azithromycin, a commonly prescribed antibiotic during pregnancy, has raised significant concerns about fetal toxicity. The placenta is essential for fetal growth and development. However, the effects of prenatal azithromycin exposure(PAzE) on placental development and function remain unclear.
Methods:
Mouse models of PAzE were established by administering the antibiotic intragastrically at varying stages (mid or late), dosages (50, 200 mg/kg·day) and courses (single or multiple). Placental evaluations encompassed histopathology and the expression of critical genes governing development and nutrient transport. Correlation between these gene alterations and insulin-like growth factor (Igf1/2) pathway were also evaluated.
Results:
PAzE promoted trophoblast proliferation and syncytialization while suppressing endothelial differentiation and placental angiogenesis, particularly under late-gestation, high-dose, and multiple-course. Notably, nutrient transport alterations showed distinct gestational stage-specific and sex-dimorphic patterns. Mid-gestation exposure upregulated glucose transporter (Glut1) in both sexes, while downregulating amino acid transporters (Lat1, Lat2) and cholesterol transporters (Abcg1, Srb1) in males. Late-gestation multi-course exposure upregulated Glut1 and cholesterol transporter (Abca1) across sexes, with males exhibiting additional activation of Glut3 and Srb1. Single-course exposure induced cross-sex upregulation of Glut1 and Abca1. In males, PAzE-induced changes in placental developmental markers (Caspase3, Syna, Synb, Plgf, Vegf) correlated with the GC/IGF1 axis, while transporter alterations (Glut1, Glut3, Abca1, Srb1) were associated with IGF2/IGF1R.
Discussion:
PAzE impairs placental development and function in a stage-, dose-, and duration-dependent manner, with potential sex-specific susceptibilities. These effects may be mediated by IGF1/IGF2 pathways. Our findings provide novel perspectives into azithromycin-induced developmental toxicity and refine precise therapeutic strategies during pregnancy.
